Vial cap and method for removing matrix components from a liquid sample

ABSTRACT

A vial cap for removing a matrix component from a liquid sample is described. The vial cap includes a cap body, an inlet portion, and an outlet portion. The cap body is configured to have a slidable gas and liquid seal with a side wall of a sample vial. The inlet portion includes a counterbore section that holds a filter plug. The filter plug includes a polyethylene resin and a material selected from the group consisting of an ion exchange material and a reversed-phase material. The vial cap is adapted for solid phase extraction for use in an autosampler with a plurality of sample vials.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a continuation under 35 U.S.C. §120 andclaims the priority benefit of co-pending U.S. patent application Ser.No. 16/677,089, filed Nov. 7, 2019, which is a continuation of U.S.patent application Ser. No. 14/586,339, filed Dec. 30, 2014. Thedisclosure of each of the foregoing applications is incorporated hereinby reference.

BACKGROUND

Chromatography is a widely used analytical technique for the chemicalanalysis and separation of molecules. Chromatography involves theseparation of one or more analyte species from other matrix componentpresent in a sample. A stationary phase of a chromatography column istypically selected so that there is an interaction with the analyte.Such interactions can be ionic, hydrophilic, hydrophobic, orcombinations thereof. For example, the stationary phase can bederivatized with ionic moieties that ideally will bind to ionic analytesand matrix components with varying levels of affinity. A mobile phase ispercolated through the stationary phase and competes with the analyteand matrix components for binding to the ionic moieties. The mobilephase is a term used to describe a liquid solvent or buffer solutionthat is pumped into a chromatography column inlet. During thiscompetition, the analyte and matrix components will elute off of thestationary phase as a function of time and then be subsequently detectedat a detector. Examples of some typical detectors are a conductivitydetector, a UV-VIS spectrophotometer, and a mass spectrometer. Over theyears, chromatography has developed into a powerful analytical tool thatis useful for creating a healthier, cleaner, and safer environment wherecomplex sample mixtures can be separated and analyzed for variousindustries such as water quality, environmental monitoring, foodanalysis, pharmaceutical, and biotechnology.

Under certain circumstances, a sample can have a relatively highconcentration of a matrix component compared to the analyteconcentration. This can cause an interference and prevent an accurateanalysis of the analyte within the sample. In one instance, anexcessively high matrix concentration can saturate the conductivitydetector skewing the baseline response of the analyte peak of achromatogram. In another instance, a matrix component can generate achromatographic peak that overlaps with the analyte peak, and thus,interfere with the analysis. An example of matrix component can be anion such as chloride in the trace analysis of perchlorate. As such, theliquid sample will typically be pre-treated to remove or reduce a highconcentration of a matrix component like chloride. Another example of amatrix component can be a hydrophobic species such as sodium laurylsulfate in the analysis of anions such as chloride and sulfate.

Solid phase extraction is a type of sample pre-treatment that can beused to remove matrix component from a sample. Some solid phaseextraction devices require a significant amount of pressure to pass aliquid sample through the solid phase extraction device, which is notwell-suited to automated sample pre-treatment with auto-samplers. Othersolid phase extraction devices that do not require a significant amountof pressure cannot bind a significant amount of matrix component becauseof low capacity. A relatively low dead volume is useful where there is alimited volume of a sample to pre-treat. Thus, Applicant believes thatthere is a need for solid phase extraction materials that have a highcapacity per unit volume sufficient to pre-treat a single sample,require a relatively low pressure (i.e., less than 100 PSI), and have acompact size so that it can be adapted to existing auto-samplinginstruments. Applicant also believes that the extraction material shouldbe low cost so that it is single use and disposable circumventing theneed to clean the extraction material after the extraction.

SUMMARY

A vial cap for removing a matrix component from a liquid sample andtransferring the liquid sample in a sample vial to an injection valve atthe same time is described. The vial cap includes a cap body, an inletportion, and an outlet portion. The cap body includes a liquid samplepassageway, and an outer periphery configured to have a slidable gas andliquid seal with a side wall of a sample vial. The sample vial includesa side wall, a bottom wall, and an inlet opening. The inlet portion isconfigured to receive a pressurized liquid sample from the sample vialwhere the liquid sample flows into the liquid sample passageway. Theinlet portion includes a counterbore section. The counterbore sectioncan hold a filter plug. The filter plug includes a polyethylene resinand a material selected from the group consisting of an ion exchangematerial and a reversed-phase material. In another embodiment, thematerial may be a combination of an ion exchange material and areversed-phase material. The outlet portion can be configured to outputthe liquid sample from the liquid sample passageway that has passedthrough the filter plug. The outlet portion includes a plunger sectionconfigured to receive a downward force into a sample vial to pressurizethe liquid sample within the sample vial. The matrix component isselected from the group consisting of an ionic species, a hydrophobicspecies, and a combination thereof.

In regards to the vial cap described above, the reversed-phase materialis configured to bind an ion pairing agent. The reversed-phase materialis also configured to bind the matrix component where the matrixcomponent is hydrophobic.

In regards to the vial cap described above, the polyethylene resin caninclude a high density polyethylene and the ion exchange material caninclude a crosslinked styrene sulfonate. Alternatively, the polyethyleneresin can include a high density polyethylene and the ion exchangematerial can include a crosslinked copolymer of a vinylbenzylchlorideand a divinylbenzene where the crosslinked copolymer is quaternized witha trimethylamine. In another embodiment, the polyethylene resin caninclude a high density polyethylene and the ion exchange material caninclude a crosslinked copolymer of a chloromethylated styrenequaternized with a tertiary amine and a divinylbenzene.

In regards to the vial cap described above, the polyethylene resin caninclude a high density polyethylene and the reversed-phase material caninclude a divinylbenzene resin treated with an ion pairing agentselected from the group consisting of a hexane sulfonate, octanesulfonate, dodecane sulfonate, tetrapropylammonium, tetrabutylammonium,tetrapentylammonium, trifluoroacetate, heptafluorobutyrate,dodecylsulfate, and combinations thereof.

In regards to the vial cap described above, the polyethylene resin caninclude a high density polyethylene and the ion exchange material caninclude a crosslinked styrene sulfonate treated with an anion exchangelatex.

In regards to the vial cap described above, the polyethylene resin caninclude a high density polyethylene and the ion exchange material caninclude a positively charged crosslinked polymer treated with a cationexchange latex. The positively charged crosslinked polymer is selectedfrom the group consisting of a copolymer of a vinylbenzylchloride and adivinylbenzene where the crosslinked copolymer that is quaternized witha trimethylamine, and a crosslinked copolymer of a chloromethylatedstyrene quaternized with a tertiary amine and a divinylbenzene.

In regards to the vial cap described above, the plunger section is asocket configured to receive a plunger. The plunger is configured toapply a downward force to the vial cap and transfer the liquid samplethrough a hollow portion of the plunger.

A method of removing a matrix component from a liquid sample isdescribed using one of the above described vial caps. The methodincludes adding the liquid sample to a sample vial. The vial cap ispushed through the inlet opening of the sample vial towards the bottomwall to pressurize the liquid sample within the sample vial. The liquidsample is displaced into the inlet portion, through the filter plug, andout of the outlet portion. At the same time of the displacing, a portionof the matrix component is removed from the liquid sample with thefilter plug.

In regards to the above method, the pressure within the sample vial isless than 100 PSI.

In regards to the above method, it further includes disposing the vialcap along with the filter plug.

In regards to the above method, the liquid sample includes particles,and the method further includes the removing of a portion of theparticles from the liquid sample with the filter plug.

In regards to the above method, the removed portion of the matrixcomponent is greater than 50% of the matrix component present in theliquid sample before the liquid sample displacing.

In regards to the above method, it further includes loading a sampleloop on an injection valve with the displaced liquid sample. The liquidsample can then be injected in the sample loop to a chromatographicseparation device. At least one analyte is separated from the matrixcomponents in the liquid sample on the chromatographic separationdevice. An analyte separated from the matrix components is detected at adetector.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are incorporated herein and constitutepart of this specification, illustrate presently preferred embodimentsof the invention, and, together with the general description given aboveand the detailed description given below, serve to explain features ofthe invention (wherein like numerals represent like elements).

FIG. 1 is a flow chart illustrating a method of removing a matrixcomponent from a liquid sample using a vial cap containing a filterplug.

FIG. 2 illustrates a cross-sectional view of a sample delivery needle, avial cap, and a sample vial where the vial cap and the sample deliveryneedle are in an unengaged state.

FIG. 3 illustrates a cross-sectional view of the sample delivery needleengaged with the vial cap where the sample delivery needle is partiallydeployed to dispense fluid out of the sample vial.

FIG. 4 shows an expanded cross-sectional view of the sample deliveryneedle engaged with the vial cap that illustrates a position of a filterplug that removes matrix components. The expanded cross-sectional viewof FIG. 4 approximately corresponds to circle 4 of FIG. 3.

FIG. 5 is a partial perspective view of an autosampler suitable fordispensing liquid samples from a plurality of sample vials and that usethe filter plugs described herein for removing matrix components.

DETAILED DESCRIPTION OF EMBODIMENTS

The following detailed description should be read with reference to thedrawings, in which like elements in different drawings are identicallynumbered. The drawings, which are not necessarily to scale, depictselected embodiments and are not intended to limit the scope of theinvention. The detailed description illustrates by way of example, notby way of limitation, the principles of the invention. This descriptionwill clearly enable one skilled in the art to make and use theinvention, and describes several embodiments, adaptations, variations,alternatives and uses of the invention, including what is presentlybelieved to be the best mode of carrying out the invention. As usedherein, the terms “about” or “approximately” for any numerical values orranges indicate a suitable dimensional tolerance that allows the part orcollection of components to function for its intended purpose asdescribed herein.

A filter plug can be a porous material used to filter a liquid sample.In an embodiment, matrix components can be retained by the filter plugso that the filtered liquid sample (i.e., filtrate) has a substantialportion of the matrix components removed. In an embodiment, asubstantial portion or substantially all may represent greater than 50%.In addition to removing matrix components, the filter plug can alsoremove particles from the liquid sample at the same time. The filterplug can include a polyethylene resin and a material such as an ionexchange material, a reversed-phase material, or a combination thereof.The ion exchange material may be an anion exchange material or a cationexchange material. The ion exchange material is configured to bindanions or cations from the liquid sample. The reversed-phase material isconfigured to bind hydrophobic material from the liquid sample.

In an embodiment, polyethylene resin can be in the form of particles,which are fused together at elevated temperatures to bind ion exchangeparticles or reversed-phase particles. The polyethylene resin may be ahigh density polyethylene (HDPE). The density of HDPE can range from0.93 to 0.97 g/cm³. Although the density of HDPE is only marginallyhigher than that of low density polyethylene (LDPE), HDPE has littlebranching, giving it stronger intermolecular forces and tensile strengththan LDPE. In an alternative embodiment to HDPE resin, other materialsthat may be suitable for use in the filter plugs described hereininclude polypropylene resin, polytetrafluoroethylene (PTFE),polyvinylidene fluoride (PVDF), ethyl vinylacetate (EVA), polycarbonateand polycarbonate alloys, nylon 6, thermoplastic polyurethane (TPU), andpolyether sulfone (PES).

The ion exchange resin may be one of the following types such as astrong cation exchange, weak cation exchange, strong anion exchange, andweak anion exchange. In an embodiment of a cation exchange resin, theresin may be in a salt form of a cation exchange resin such as, forexample, a sodium form.

The ion exchange resin includes a substrate that is insoluble in waterand typically in the form of approximately spherical beads. In anembodiment, the beads may have a diameter ranging from about 2 micronsto about 100 microns, preferably ranging from about 2 microns to about50 microns, and more preferably ranging from about 10 microns to about35 microns. The ion exchange resin may have a pore size ranging fromabout 10 angstroms to about 2000 angstroms.

In an embodiment, the ion exchange material may include a crosslinkedstyrene sulfonate particle. As an example, the particle size can beabout 35 microns in diameter and be in the sodium form. The sulfonategroups on the particles act as the cation exchange groups.

In regards to anion exchange material, a crosslinked copolymer of avinylbenzylchloride and a divinylbenzene can be used where thecrosslinked copolymer is quaternized with a tertiary amine.Alternatively, the anion exchange material can be prepared viachloromethylation of a crosslinked copolymer of styrene anddivinylbenzene where the crosslinked copolymer is quaternized with atertiary amine. Examples of tertiary amines are trimethylamine anddimethylethanolamine. As an example, the particle size can be about 35microns in diameter and be in the chloride form.

In an embodiment, the reversed-phase material may be a copolymer ofstyrene and divinyl benzene. More broadly, the reversed-phase polymercan be synthesized from a wide variety of polyunsaturated monomersincluding divinylbenzene, trivinylbenzene and the like, and thepreferred monoethylenically unsaturated monomers including styrene, theo, m, and p-methyl styrenes, and o, m, and p-ethyl styrenes,ethylvinylbenzene, vinylnaphthalene and vinyltoluene. Suitablereversed-phase polymers can also be derived from aliphaticpolyunsaturated monomers such as diacrylates and dimethacrylates,including ethylene glycol diacrylate, ethylene glycol dimethacrylate,trimethylolpropane trimethacrylate, neopentyl glycol dimethacrylate,divinylketone, divinyl sulfide, allyl acrylate, diallyl maleate, diallylfumarate, and the like. Such reversed-phase polymers can also besynthesized as copolymers with monoethylenically unsaturated aliphaticmonomers include esters of acrylic acid, such as methyl, ethyl andpropyl acrylate, and the corresponding esters of methacrylic acid,wherein the ester group contains 1-10 carbon atoms. The preferredreversed phase polymers are based on macroreticular copolymers ofstyrene and divinylbenzene (about 99-2 wt. % styrene, balancedivinylbenzene). The foregoing ranges are on the basis of 100% activemonomers. When commercial grades of divinylbenzene are used, about20-50% of the divinylbenzene is ethylvinylbenzene and it is conventionalto include the ethylvinylbenzene with the styrene or other monovinylmonomer when specifying the proportion of styrene or other monovinylmonomer. The reversed-phase material may also be based on surfacechemical modification of inorganic materials such as silica, alumina,zirconia and the like such that the surface of the inorganic material ishydrophobic. Examples of such reversed phase materials based oninorganic substrates include porous silica particles which have beensurface modified with any of a wide variety of commercially availablealkylsilanes such as octadecylsilanes, dodecylsilanes, octylsilanes,butylsilanes or methylsilanes.

In another embodiment, the reversed-phase material may include adivinylbenzene resin treated with an ion pairing agent. Exemplary ionpairing may include hexane sulfonate, octane sulfonate, dodecanesulfonate, tetrapropylammonium, tetrabutylammonium, tetrapentylammonium,trifluoroacetate, or heptafluorobutyrate, dodecylsulfate. Otherexemplary ion pairing agent may include alkyl sulfates where the alkaneis between five and 18 carbons in length, alkyl sulfonates where thealkane is between five and 18 carbons in length, linear alkylbenzenesulfonates where the alkane substituent is between five and 18 carbonsin length, branched alkylbenzene sulfonates where the alkane substituentis between five and 18 carbons in length, perfluorocarboxylic acidswhere the carbon backbone is between 1 and 12 carbons in length,symmetrical quaternary compounds where each of the four alkanes attachedto the quaternary nitrogen is between five and 18 carbons in length,unsymmetrical quaternary compounds where three of the alkyl groupsattached to the quaternary nitrogen are methyl substituents while thefourth alkyl group attached to the quaternary nitrogen is between fiveand 18 carbons in length, unsymmetrical quaternary compounds where twoof the groups attached to the quaternary nitrogen are methylsubstituents, a benzyl group is attached to the quaternary nitrogen andthe fourth substituent group attached to the quaternary nitrogen isbetween five and 18 carbons in length, or unsymmetrical quaternarypyridinium compounds where the substituent group attached to thepyridinium nitrogen is between five and 18 carbons in length. It shouldbe noted that the ion pairing agent can be in a salt form, an acid form,or a base form.

The ion pairing agent hexanesulfonic acid is an example that providescation exchange functionality. Alternatively, the divinylbenzene resincan be treated with the ion pairing agent tetrabutylammonium hydroxide,which is an example that provides anion exchange functionality. Thedivinylbenzene resin can be a copolymer with materials such asdivinylbenzene and polystyrene, and have a diameter of about 35 microns.The divinylbenzene resin is typically hydrophobic in nature. An ionpairing agent such as hexanesulfonic acid or tetrabutylammoniumhydroxide can be paired to the hydrophobic surface of the divinylbenzeneresin and create ion exchange sites. The filter plug can be made withpolyethylene resin and divinylbenzene resin. Next, an ion pairing agentin a liquid solution can be filtered through the filter plug so that theion pairing agent can attach to the divinylbenzene resin.

In another embodiment, the ion exchange material may include crosslinkedstyrene sulfonate particles treated with anion exchange latex. The anionexchange latex can include a quaternary amine group and have a diameterof about 360 angstroms. The filter plug can be made with polyethyleneresin and crosslinked styrene sulfonate particle. Next, an anionexchange latex in a liquid solution can be filtered through the filterplug so that the latex can attach to the crosslinked styrene sulfonateparticles. An example of anion exchange latex having quaternary aminegroups can be found in U.S. Pat. No. 5,324,752, which is herebyincorporated by reference herein.

In another embodiment, the ion exchange material may include an anionexchange material such as a chloromethylated, crosslinked copolymer ofstyrene and divinylbenzene. The crosslinked copolymer is quaternizedwith a tertiary amine and subsequently treated with cation exchangelatex. The cation exchange latex can include a sulfonated styrene groupand have a diameter of about 200 nanometers. The filter plug can be madewith polyethylene resin and an anion exchange material. Next, a cationexchange latex in a liquid solution can be filtered through the filterplug so that the latex can attach to the anion exchange particles. Anexample of cation exchange latex having sulfonated styrene groups can befound in U.S. Pat. No. 5,324,752, which is hereby incorporated byreference herein.

The matrix component binding material may be physically entrapped withina void volume in the fused polyethylene. Alternatively, the matrixcomponent binding material can be bound to the polyethylene by achemical bond or by an affinity to the polyethylene. In an embodiment,the polyethylene may be in the form of approximately spherical beads andfused together by heat. The matrix component binding material can be inthe form of a resin substrate. As used herein, a resin or material canrefer to a polymeric substrate and can be a plurality of particles.

The matrix component binding filter plugs can have a high capacity witha capacity per unit volume of greater than 0.05 milliequivalents percubic centimeter (mEq/cc), and preferably ranging from about 0.14 mEq/ccto about 0.70 mEq/cc. The term milliequivalent refers to the equivalentsof charged ions that can be bound to the matrix component binding filterplugs divided by a thousand.

In an embodiment, the matrix component binding filter plugs has a flowrate ranging from about 0.5 mL per minute to about 10 mL per minute,preferably from about 0.5 mL per minute to about 5 mL per minute, andmore preferably from about 2 mL per minute to about 5 mL per minute at apressure of 50 pounds per square inch or less where the matrix componentbinding filter plug is in the form of a cylinder with a diameter ofabout 5 millimeters and a length of about 10 millimeters.

The matrix component binding filter plugs can have a porosity rangingfrom about 50% to about 90%, where the porosity is based on the equation[(gram of water+gram of resin)/(gram of water+gram of resin+gram oforganic phase)]×100%.

The matrix component binding filter plugs can also be characterized interms of permeability. The matrix component binding filter plugs canhave a range of approximately cylindrical sizes such as an outerdiameter ranging from about 0.4 mm to about 20 mm, and a length rangingfrom about 6 mm to about 20 mm. The backpressure may be about 50 poundsper square inch and the flow rate through the matrix component bindingfilter plug may range from about 1 to about 5 mL/min. An equation forpermeability can be calculated based on Equation 1.

Δp=u ηL/B   (Eq. 1)

The terms Δp is a backpressure, u is a linear velocity of the sampleflowing through the filter, η is a viscosity of the liquid sample, L isa length of the filter, and B is a permeability of the matrix componentbinding filter plug. Based on Eq. 1 and the aforementioned parameters,the matrix component binding filter plugs can have a permeabilityranging from about 1×10⁻¹¹ m² to about 1×10⁻¹⁶ m².

Liquid samples can be filtered through the filter plugs described hereinto remove matrix components from a sample in an automated format at lowpressures and short cycle times. For convenience, the filter plugs canbe relatively low cost, disposable, and have sufficient capacity to binda substantial portion of matrix components for at least one samplealiquot. The following will describe a vial cap that is configured tohold the filter plug.

FIG. 2 illustrates a cross-sectional view of a plunger 33, a vial cap54, and a sample vial 44 where vial cap 54 and plunger 33 are in anunengaged state. Plunger 33 is configured to bind to the vial cap 54.The vial cap 54 is configured to provide a seal at a side wall of thevial cap 54. Plunger 33 and the vial cap 54 together can be configuredto have a piston cylinder mechanism with the sample vial 44 to dispensethe liquid sample. A similar sample filtering apparatus is describedU.S. Pat. No. 4,644,807 and US Pre-Grant Publication No. 20100224012,which are hereby incorporated by reference herein; however, the filterin this reference was used to remove particulates and/or reduceevaporation.

Referring to back to FIG. 2, vial cap 54 includes a cap body 202, aninlet portion 204, and an outlet portion 206. Cap body 202 includes aliquid sample passageway 208. Cap body 202 has an outer peripheryconfigured to have a slidable gas and liquid seal with a side wall ofsample vial 44. Inlet portion 204 is configured to receive a pressurizedliquid sample from sample vial 44 where the liquid sample flows intoliquid sample passageway 208. Vial cap 54 is configured to cap the openended portion of the sample vial 44. Further, the vial cap 54 is alsoconfigured to be slidingly engaged with and to seal the side wall of thesample vial 44. The vial cap 54 has a generally concave portion thatcooperatively mates with a generally convex lowermost portion of thesample vial 44.

Inlet portion can include a counterbore section 210 for holding a filterplug described herein. Counterbore section 210 is a cylindrical holeadjacent to outlet portion 206. The diameter of counterbore section 210is greater than outlet portion 206. In an embodiment, the diameter ofcounterbore section 210 is sized to form a friction fit to hold acylindrically shaped filter plug, as illustrated in FIG. 4.Alternatively, the filter plug can be mounted to the counterbore sectionwith other types of fasteners.

Outlet portion 206 is configured to output the liquid sample from liquidsample passageway 208 that has passed through filter plug 42. Outletportion 206 includes a plunger section 70 configured to receive adownward force into sample vial 44 to pressurize the liquid samplewithin sample vial 44. Plunger section 70 includes a socket configuredto receive a plunger 33. Plunger 33 can have a geometric shape proximateto a tip 68 that mates with the socket of plunger section 70 to form afluid tight seal, as illustrated in FIGS. 2 to 4. Plunger 33 isconfigured to apply a downward force to vial cap 54 and transfer theliquid sample through a hollow portion of plunger 33

The vial cap 54 does not begin to move until tip 68 of the plunger isfully seated in a plunger portion 70 (best shown in FIG. 3). When theplunger 33 begins to deploy, any air trapped in the sample vial 44 abovethe sample is discharged first. Once the delivery of the liquid sample46 begins, it continues until the required sample amount has been drawnor the sample vial 44 is empty. In various embodiments, the sample vialand vial cap are configured to reduce “dead space” in the sample vial.The bottom of the exemplary vial has a shape corresponding to the capsuch that substantially all of the fluid is displaced from the vial whenthe cap contacts the bottom.

Sample vial 44 and vial cap 54 are configured such that when the plunger33 is fully deployed causing the vial cap 54 to remain in the lowestdisplacement position in the sample vial 44. Thus, the needle pressesthe vial cap 54 into the sample vial 44 but is withdrawn from the samplevial 44 without the vial cap 54. The vial cap remains in the sample vialwith the sample pressurized below the cap. In one embodiment, the vialincludes a bottom portion configured to fit tightly with vial cap 54.When plunger is retracted, the vial cap can be held in the bottomportion of the vial due to the tight fit and the plunger separates fromthe vial cap. After displacing the liquid sample through the filterplug, the vial cap along with the filter plug can be disposed as wasteand not re-used.

Plunger 33 can also be referred to as a sample delivery needle orplunger needle and has a hollow cylindrical rod shaped structure. At oneend of plunger 33, there is a needle tip 68. The other opposing end ofplunger 33 can be used to transfer the liquid sample 46 to an analyticalinstrument.

Now that the vial cap have has described, the following will describe amethod of using a vial cap to filter out and remove matrix componentsfrom a sample. An analyst will often have a large number of sample vialscontaining samples that need to be analyzed. However, before beginningthe analysis testing, a sample pre-treatment may need to be performed toremove matrix components that can interfere with the analysis. Adding amatrix binding agent to the sample vial, mixing the sample vial, andfiltering the matrix binding agent from the sample is a manual processthat is time consuming and laborious. To implement an automated process,the matrix component binding filter plug can be used as a filter that isincorporated into the vial cap. The sample vial and vial cap areconfigured so that liquid flows through the vial cap and the filter at arelatively low pressure while at the same time efficiently binding asubstantial portion of the matrix components. The pressure range forfiltering sample may range from about 10 pounds per square inch to about100 pounds per square inch.

FIG. 1 is a flow chart illustrating a method 100 of removing a matrixcomponent from a liquid sample using a vial cap containing one of thematrix component binding filter plugs described herein. In a step 102, aliquid sample is added to a sample vial. Next, a vial cap is pushedthrough an inlet opening of the sample vial towards the bottom wall topressurize the liquid sample within the sample vial, as shown in a step104. The liquid sample is displaced into the inlet portion, through thefilter plug, and out of the outlet portion, where the filter plugincludes a polyethylene resin and a matrix component binding material(e.g., ion exchange material or a reversed-phase material), as shown ina step 106. At the same time of the displacing of step 106, a portion ofthe ions is removed from the liquid sample with the filter plug, asshown in a step 108. In an embodiment, about 50% or more of the matrixcomponents can be removed from the liquid sample with a filter plug.

Once the sample has been pretreated to remove interfering matrixcomponent, it can be subsequently analyzed with analyticalinstrumentation. After removing liquid sample 46 from the sample vial44, the liquid sample 46 can be loaded onto a sample loop of aninjection valve. Next, liquid sample from the sample loop can beinjected into a chromatographic separation device. At least one analytefrom the liquid sample can be separated from matrix components in thechromatographic separation device and the analyte can be detected at adetector.

FIG. 5 is a partial perspective view of an autosampler 30 suitable fordispensing liquid samples from a plurality of sample vials and for usewith filter plugs described herein. Autosampler 30 is typically usedwhen a large number of samples need to processed in an automated manner.A plurality of sample vials can be loaded on autosampler 30 in an arrayor carousel format. FIG. 5 illustrates a carousel of sample vial sockets47 configured to hold a plurality of sample vials. A fluid deliveryassembly 32 is configured to deploy and retract the plunger needle forone sample vial at a time as shown in a dotted circle 1B of FIG. 5. Thecarousel can increment a position by rotating around a hub with a drivemotor 65 so that liquid can then be transferred from a subsequent samplevial. Autosampler 30 also includes a control system 74 that has amicroprocessor 75 and a memory 77. Examples of commercially availableautosamplers are the AS-DV, AS40, and ASM from Thermo Fisher Scientific.

EXAMPLE 1

This Example illustrates the removal of divalent cations using acation-exchange filter plug. A cylindrical filter plug of blended highdensity polyethylene (HDPE) and approximately 10 mg fully sulfonated,16% crosslinked styrenesulfonate, sodium-form resin with a particlediameter of 35 μm was inserted into the counterbore portion of a vialcap. The cylindrical filter plug had an approximate diameter of 5 mm anda length of about 10 mm. The assembled vial cap with the cation exchangefilter plug was sonicated in deionized water for 5 minutes.

A standard sample of six cations including 0.05 mg/L lithium, 0.2 mg/Lsodium, 0.4 mg/L ammonium, 0.2 mg/L potassium, 0.2 mg/L magnesium and 1mg/L calcium was loaded into a 5 mL sample vial. The assembled vial capwas inserted into the filled sample vial. Five milliliters of a sample(see Table 1) was pushed up through the filter plug in the vial cap anddirected to a sample loop of an ion chromatograph for analysis usingcation exchange chromatography. An eluent of 20 mM methanesulfonic acidwas flowed at 0.5 mL/min through a cation exchange analytical column(part no. CS12A, 150×3-mm I.D., commercially available from ThermoFisher Scientific) and an electrolytic suppressor (part no. CSRS 300,2-mm I.D., commercially available from Thermo Fisher Scientific)followed by an electrical conductivity detector cell. The resultingchromatography peaks were integrated using CHROMELEON™ chromatographydata system software (version 6.8, commercially available from ThermoFisher Scientific).

Table 1 shows the results from a series of samples pretreated with thefilter plug of Example 1 and analyzed using cation exchangechromatography.

Area, Area, Sodium % Calcium % Sample Description μS*min Removed μS*minRemoved 1 6 Cation Standard 0.039 — 0.18 — with no solid phaseextraction 2 Water Flowed 0.108 — 0.004 — Through Filter Plug of Ex. 1 36 Cation Standard 1.34 * 0.007 61 Flowed Through Filter Plug of Ex. 1*Sodium increase due to displacement from the cation exchange resin bycalcium

In Sample 1 of this Example, the six cation standard was analyzed in theion chromatograph without a prior solid phase extraction where theresulting peak areas were proportional of the concentration of sodiumand calcium in the six cation standard.

In Sample 2 of this Example, five milliliters of deionized water wasflowed through the filter plug of this Example. This is a wash of thefilter plug before use to remove calcium. Next, the filtered liquidswere subsequently analyzed with the ion chromatograph. The amount ofmeasured sodium was relatively high because the ion exchange material inthe filter plug was in the sodium form. The amount of calcium wasrelatively low with respect to Sample 1 of this Example, but indicatedthat some residual calcium was on the filter plug.

In Sample 3 of this Example, five milliliters of the six cation standardwas flowed through the filter plug of this Example. Next, the filteredliquids were subsequently analyzed with the ion chromatograph. Theamount of measured sodium was relatively high because the ion exchangematerial in the filter plug was in the sodium form and the sodium wasdisplaced by the more highly retained cations, most notably, calcium.The amount of calcium was decreased by 61% with respect to Sample 1 ofthis Example, which indicated that a substantial amount was retained bythe filter plug.

EXAMPLE 2

This Example illustrates the use of an ion-pairingreagent-functionalized reversed phase filter cap to remove cations froma sample. A cylindrical plug comprising blended high densitypolyethylene (HDPE) and 10 mg of 55% divinylbenzene resin with aparticle diameter of 35 μm was inserted into the counterbore portion ofa vial cap. The cylindrical filter plug had an approximate diameter of 5mm and a length of about 10 mm. The assembled vial cap with the cationexchange filter plug was placed on a vacuum station and 2 mL of methanolwas pushed up through the filter plug. Next, the assembled vial cap wassequentially flushed with a series of liquids, which 2 mL deionizedwater, 2 mL of 100 mM hexanesulfonic acid (HSA), and another aliquot ofdeionized water.

A standard sample of four cations including 5 ppb lithium, 20 ppbsodium, 20ppb magnesium and 100 ppb calcium was loaded into a samplevial. The assembled vial cap was inserted into the filled sample vial.Two milliliters of a sample (see Table 2) was pushed up through thefilter plug in the vial cap and directed to the ion chromatograph forcation exchange analysis. The cation exchange chromatography systemconditions were similar to Example 1.

Table 2 shows the results from a series of samples pretreated with thefilter plug of Example 2 and analyzed using cation exchangechromatography.

Area, Area, Area, Sodium % Magnesium % Calcium % Sample Description μS *min Removed μS * min Removed μS * min Removed 1 4 Cation Standard 0.01 —0.028 — 0.007 — with no solid phase extraction 2 Deionized water na — —— — — blank 3 4 Cation Standard 0.01 0 0.029 0 0.007 0 Flowed ThroughFilter Plug of Ex. 2 without HSA 4 4 Cation Standard 0.01 0 0.011 620.002 71 Flowed Through Filter Plug of Ex. 2 with HSA

In Sample 1 of this Example, the four cation standard was analyzed inthe ion chromatograph without a prior solid phase extraction where theresulting peak areas were proportional of the concentration of sodium,magnesium, and calcium in the 4 cation standard.

In Sample 2 of this Example, two milliliters of deionized water wasanalyzed in the ion chromatograph without a prior solid phaseextraction. The amounts of sodium, magnesium, and calcium measuredthrough the chromatographic analysis were negligible.

In Sample 3 of this Example, two milliliters of the four cation standardwas flowed through a filter plug without HSA treatment of this Example.Next, the filtered liquids were subsequently analyzed with the ionchromatograph. The measured sodium, magnesium, and calcium levels wereessentially the same as Sample 1 indicating that cations were notretained by the filter plug without HSA treatment.

In Sample 4 of this Example, two milliliters of the four cation standardwas flowed through the filter plug with HSA treatment of this Example.Next, the filtered liquids were subsequently analyzed with the ionchromatograph. The amount of magnesium and calcium was decreased by 62%and 71%, respectively. This decrease was calculated relative to thecation levels in Sample 1 of this Example, which indicated that asubstantial amount of divalent cations was retained by the filter plugwith HSA treatment. The monovalent cation sodium was not retained by thefilter plug of this Example, which was indicated by the approximate samelevel of sodium measured in Sample 1 and Sample 4.

EXAMPLE 3

This Example illustrates the use of an anion exchange filter plugprepared with latex particles to remove anions from a sample. Acylindrical filter plug of blended high density polyethylene (HDPE) andapproximately 10 mg fully sulfonated, 16% crosslinked styrenesulfonate,sodium-form resin with a particle diameter of 35 μm was inserted intothe counterbore portion of a vial cap as described in Example 1. Thecylindrical filter plug had an approximate diameter of 5 mm and a lengthof about 10 mm.

Five milliliters of deionized water was flowed through the filter plugusing a vacuum. Five milliliters of a anion exchange latex, prepared ina manner similar to the description in example 3 of U.S. Pat. No.5,324,752, was flowed through the filter plug using vacuum, followed by5 milliliters of deionized water, 5 milliliters of a mixture of 50%methanol/50% deionized water, and 5 milliliters of deionized water.

A standard sample of six anions including 0.02 mg/L fluoride, 0.03 mg/Lchloride, 0.1 mg/L nitrate, 0.15 mg/L sulfate, 0.15 mg/L phosphate, and0.01% acetic acid was loaded into a 5 mL sample vial. The assembled vialcap was inserted into the filled sample vial. Five milliliters of sample(see Table 3) was pushed through the filter plug in the vial cap anddirected to the ion chromatograph for an ion exchange analysis. Aneluent of 40 mM potassium hydroxide flowed at 0.3 mL/minute through ananion exchange analytical column (part no. A515, 150×3 mm I.D.) and anelectrolytic suppressor (part no. ASRS 2-mm) both supplied by ThermoFisher Scientific. An electrical conductivity detector cell was used tomeasure the anions.

Table 3 shows the results from a series of samples pretreated with thefilter plug of Example 3 and analyzed using anion exchangechromatography.

Area, Area, Sulfate % Phosphate % Sample Description μS*min RemovedμS*min Removed 1 6 Anion Standard 0.15 — 0.03 — With No Solid PhaseExtraction 2 Water Flowed 0.005 — 0 — Through Filter Plug of Ex. 3 3 6Anion Standard 0.06 60 0 100 pH 5 Flowed Through Filter Plug of Ex. 3

In Sample 1 of this Example, the six anion standard was analyzed in theion chromatograph without a prior solid phase extraction where theresulting peak areas were proportional of the concentration of sulfateand phosphate in the six anion standard.

In Sample 2 of this Example, five milliliters of deionized water wasflowed through the filter plug of this Example. Next, the filteredliquids were subsequently analyzed with the ion chromatograph. Arelatively low amount of sulfate was measured indicating that someresidual sulfate was likely on the filter plug. No phosphate wasmeasured from the filtered water sample.

In Sample 3 of this Example, five milliliters of the six anion standardwas flowed through the filter plug of this Example. Next, the filteredliquids were subsequently analyzed with the ion chromatograph. Theamount of sulfate was decreased by 60% with respect to Sample 1 of thisExample, which indicated that a substantial amount was retained by thefilter plug. Similarly, the amount of phosphate was decreased by 100%with respect to Sample 1 of this Example, which indicated that asubstantial amount was retained by the filter plug.

EXAMPLE 4

This Example illustrates the use of a reversed-phase filter plugprepared with divinylbenzene resin to remove hydrophobic material suchas sodium lauryl sulfate (SLS) from an aqueous sample. A cylindricalplug from Example 2 was used in a vial cap for this example.

The assembled vial cap was inserted into the filled sample vial. Fivemilliliters of a 100 mg/L sodium lauryl sulfate sample was pushed upthrough the filter plug in the vial cap and directed to the liquidchromatograph for surfactant analysis. An eluent of 75% acetonitrile and25% of 100 mM ammonium acetate at pH 5.4 was flowed at 0.25 mL/minthrough a reversed phase analytical column (part no. Acclaim Surfactant,150×2-mm I.D., commercially available from Thermo Fisher Scientific)followed by detection using a mass spectrometer (part no. MSQ Plus,commercially available from Thermo Fisher Scientific). The resultingchromatography peaks were integrated using CHROMELEONTM chromatographydata system software (version 6.8, commercially available from ThermoFisher Scientific). The amount of SLS injected into the analyticalsystem was the amount of SLS that was not captured by the filter plug inthe vial cap. This amount corresponded to a removal of 98% of the SLSfrom the sample. The removal of the matrix components in this Exampledemonstrates that analysis of common anions such as chloride and sulfatecan be performed.

While preferred embodiments of the present invention have been shown anddescribed herein, it will be apparent to those skilled in the art thatsuch embodiments are provided by way of example only. Numerousvariations, changes, and substitutions will now occur to those skilledin the art without departing from the invention. While the invention hasbeen described in terms of particular variations and illustrativefigures, those of ordinary skill in the art will recognize that theinvention is not limited to the variations or figures described. Inaddition, where methods and steps described above indicate certainevents occurring in certain order, those of ordinary skill in the artwill recognize that the ordering of certain steps may be modified andthat such modifications are in accordance with the variations of theinvention. Additionally, certain of the steps may be performedconcurrently in a parallel process when possible, as well as performedsequentially as described above. Therefore, to the extent there arevariations of the invention, which are within the spirit of thedisclosure or equivalent to the inventions found in the claims, it isthe intent that this patent will cover those variations as well.

What is claimed is:
 1. A vial cap for removing a matrix component from aliquid sample and transferring the liquid sample in a sample vial to aninjection valve at the same time, the vial cap comprising: a cap bodyincluding a liquid sample passageway, and an outer periphery configuredto have a slidable gas and liquid seal with a side wall of a samplevial, the sample vial including a side wall, a bottom wall, and an inletopening; an inlet portion configured to receive a pressurized liquidsample from the sample vial where the liquid sample flows into theliquid sample passageway, the inlet portion including a counterboresection, the counterbore section holding a filter plug, the filter plugcomprising high density polyethylene resin particles fused together witha material selected from the group consisting of an ion exchangematerial and a reversed-phase material, the material physicallyentrapped within a void volume in the fused high density polyethylene;an outlet portion configured to output the liquid sample from the liquidsample passageway that has passed through the filter plug, the outletportion including a plunger section configured to receive a downwardforce into a sample vial to pressurize the liquid sample within thesample vial.
 2. The vial cap of claim 1, in which the reversed-phasematerial is configured to bind an ion pairing agent in a salt form, anacid form, or a base form.
 3. The vial cap of claim 1, in which thereversed-phase material is configured to bind the matrix component wherethe matrix component is hydrophobic.
 4. The vial cap of claim 1, inwhich the matrix component is selected from the group consisting of anionic species, a hydrophobic species, and a combination thereof.
 5. Thevial cap of claim 1, in which the ion exchange material is in a saltform.
 6. The vial cap of claim 1, in which the ion exchange materialcomprises a crosslinked styrene sulfonate.
 7. The vial cap of claim 1,in which the plunger section is a socket configured to receive aplunger, the plunger configured to apply a downward force to the vialcap and transfer the liquid sample through a hollow portion of theplunger.
 8. A method of removing a matrix component from a liquid sampleusing a vial cap, the vial cap comprising: a cap body including a liquidsample passageway, an outer periphery configured to have a slidable gasand liquid seal with a side wall of a sample vial, the sample vialincluding a side wall, a bottom wall, and an inlet opening; an inletportion configured to receive a pressurized liquid sample from thesample vial where the liquid sample flows into the liquid samplepassageway, the inlet portion including a counterbore section, thecounterbore section holding a filter plug; an outlet portion configuredto output the liquid sample from the liquid sample passageway that haspassed through the filter plug, the outlet portion including a plungersection configured to receive a downward force into a sample vial topressurize the liquid sample within the sample vial, the methodcomprising: adding the liquid sample to a sample vial; pushing the vialcap through the inlet opening of the sample vial towards the bottom wallto pressurize the liquid sample within the sample vial; displacing theliquid sample into the inlet portion, through the filter plug, and outof the outlet portion, the filter plug comprising high densitypolyethylene resin particles fused together with a material selectedfrom the group consisting of an ion exchange material and areversed-phase material, the material physically entrapped within a voidvolume in the fused high density polyethylene; and at the same time ofthe displacing, removing a portion of the matrix component from theliquid sample with the filter plug.
 9. The method claim 8, in which thepressure within the sample vial is less than 100 PSI.
 10. The methodclaim 8 further comprising: disposing of the vial cap along with thefilter plug.
 11. The method claim 8, in which the liquid samplecomprises particles, the method further comprising: removing a portionof the particles from the liquid sample with the filter plug.
 12. Themethod claim 8, in which the removed portion of the matrix component isgreater than 50% of the matrix component present in the liquid samplebefore the liquid sample displacing.
 13. The method claim 8 furthercomprising: loading a sample loop on an injection valve with thedisplaced liquid sample; injecting the liquid sample in the sample loopto a chromatographic separation device; separating at least one analytefrom matrix components in the liquid sample on the chromatographicseparation device; and detecting an analyte separated from the matrixcomponents at a detector.
 14. The method of claim 8, in which the ionexchange material is in a salt form.
 15. The method of claim 8, in whichthe ion exchange material comprises a crosslinked styrene sulfonate.